Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dopamine-1 (DA-1) receptors have been found in renal tubular membranes which stimulate both adenylate cyclase and phospholipase-C activity. In renal cortical plasma membrane preparations the DA-1 agonist SKF 82526, forskolin and NaF stimulated adenylate cyclase activity. 2',5'-dideoxyadenosine inhibited basal and DA-1 agonist stimulated adenylate cyclase activity. Forskolin, NaF, dibutyryl-cyclic AMP and 2',5'-dideoxyadenosine had no effect on basal or DA-1 agonist stimulated phospholipase-C activity in these membranes. These studies indicate that DA-1 agonist stimulates adenylate cyclase and phospholipase-C activities independently. Phospholipase-C activity was also increased by the nonhydrolyzable GTP analog, guanosine-5'-O-(3-thiophosphate). When DA-1 agonist and guanosine-5'-O-(3-thiophosphate) were added together there was a slight but significant increase in phospholipase-C activity. This increase was inhibited in the presence of guanosine-5'-O-(2-thiodiphosphate). DA-1 stimulated phospholipase-C activity was found to be insensitive to both cholera and pertussis toxins. The present studies indicate a cyclic AMP independent transduction pathway for DA-1 receptor mediated through a guanine nucleotide regulatory protein associated phospholipase-C.
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PMID:The dopamine-1 agonist, SKF 82526, stimulates phospholipase-C activity independent of adenylate cyclase. 256 86

The heat-stable enterotoxin (STa) of Escherichia coli causes intestinal secretion by stimulating guanylate cyclase, an enzyme believed to be distinct from the STa receptor. Pertussis toxin (PT) has been reported to block the ability of STa to stimulate guanylate cyclase in rat intestinal mucosa (S. A. Epstein, R. A. Giannella, and H. J. Brandwein, FEBS Lett. 203:44-48, 1986). This suggested that a guanine nucleotide regulatory protein (G protein) coupled the STa receptor to guanylate cyclase, a function not previously recognized for G proteins. We sought to explore this phenomenon and, if possible, to identify this G protein. Initial experiments with the human colon carcinoma cell line T84 revealed that higher-than-expected concentrations (1 micrograms/ml) of PT were needed to intoxicate cells, as assessed by ADP-ribosylation of endogenous PT substrate, but that 99 to 100% intoxication could be achieved. Homogenates made from fully intoxicated cells did not differ from controls in basal or STa-stimulated guanylate cyclase activity, and cyclic GMP accumulation in intact T84 cells was not changed by PT treatment. We conclude that a PT-sensitive G protein is not involved in the stimulation of cyclic GMP production by the enterotoxin STa.
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PMID:Failure of pertussis toxin to inhibit activation of guanylate cyclase by the heat-stable enterotoxin of Escherichia coli (STa) in the T84 cell line. 256 75

Alpha 2-adrenergic inhibition of adenylate cyclase in bovine ciliary processes and rabbit iris ciliary body (ICB) was studied. With bovine ciliary process membrane, it was found that cAMP production in the presence of 1 microM isoproterenol was increased with increasing NaCl concentrations from 0 to 200 mM. Clonidine, an alpha 2-adrenergic agonist, produced a NaCl concentration-dependent inhibition of cAMP production in the presence of isoproterenol with a maximum inhibition at 200 mM NaCl (P less than 0.05). NaCl concentrations had no effect on basal adenylate cyclase activities and activity in the presence of clonidine alone. The alpha 2-adrenergic agonists, lofexidine, clonidine and p-amino-clonidine were tested for their ability to inhibit isoproterenol-stimulated adenylate cyclase in bovine ciliary process membrane in the presence of 200 mM NaCl. Their dose-response curves showed that they had similar IC50's but the maximum inhibition differed among these agonists. Clonidine was found to be a partial agonists producing 55% of the inhibition obtained with lofexidine. The specificity of inhibition of isoproterenol-stimulated adenylate cyclase by alpha 2-agonists and blockade by pertussis toxin was examined by adenine labelling in rabbit ICB. The results demonstrate that alpha 2-adrenergic receptors exert specific inhibitory effects on adenylate cyclase activity in rabbit ICB, which are mediated by an inhibition guanine nucleotide regulatory protein, Gi.
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PMID:Inhibition of adenylate cyclase in bovine ciliary process and rabbit iris ciliary body to alpha 2-adrenergic agonists. 257 79

Incubation of rat mast cells with compound 48/80 resulted in transient breakdown of phosphatidylinositol 4,5-bisphosphate, rapid generation of inositol polyphosphates, 45Ca inflow, and the arachidonic acid liberation mainly from phosphatidylcholine, eventually leading to histamine secretion. All of these processes of signaling from Ca-mobilizing receptors to degranulation were markedly inhibited by prior 2-h exposure of cells to islet-activating protein (IAP), pertussis toxin. A23187 caused 45Ca inflow and releases of arachidonic acid and histamine without inducing breakdown of inositol phospholipids. The effects of A23187, in contrast to those of compound 48/80, were not altered by the exposure of cells to IAP. Incubation of the supernatant fraction of mast cell homogenates with the active component of IAP caused the transfer of the ADP-ribosyl moiety of added [alpha-32P]NAD to a protein with Mr = 41,000. The IAP-catalyzed ADP-ribosylation of this protein was prevented by guanosine 5'-(3-O-thio)triphosphate, indicating that this IAP substrate resembles, in character, the alpha-subunit of the guanine nucleotide regulatory protein (Ni) involved in inhibition of adenylate cyclase. The degree of ADP-ribosylation of this IAP substrate was prevented progressively by pre-exposure of the homogenate-donor cells to increasing concentrations of IAP. The half-maximally effective concentrations of the toxin were 0.2 to 0.6 ng/ml for all the IAP-sensitive processes studied. Thus, the ADP-ribosylation of the Mr = 41,000 protein occurring during exposure of cells to IAP appears to be responsible for the inhibition of signaling observed. It is proposed that the alpha-subunit of Ni, or a like protein, mediates signal transduction arising from Ca-mobilizing receptors, probably prior to Ca2+ gating.
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PMID:Simultaneous inhibitions of inositol phospholipid breakdown, arachidonic acid release, and histamine secretion in mast cells by islet-activating protein, pertussis toxin. A possible involvement of the toxin-specific substrate in the Ca2+-mobilizing receptor-mediated biosignaling system. 257 78

Activation of vascular smooth muscle by angiotensin II results in the phospholipase C-mediated generation of two second messengers, inositol trisphosphate (IP3) and diacylglycerol (DG). IP3 is responsible for mobilizing calcium from endoplasmic reticulum whereas DG activates protein kinase C and ultimately Na+/H+ exchange, leading to intracellular alkalinization. The IP3/calcium signal is transient, most likely serving to initiate calcium-mediated events leading to contraction, and is attenuated by activation of protein kinase C. DG formation/protein kinase C activation is sustained and may be enhanced by the concurrent intracellular alkalinization. The delay in induction of the sustained response appears to be related to cellular processing of the angiotensin II-receptor complex. Phospholipase C activity is also modulated by a cholera toxin-sensitive, pertussis toxin-insensitive guanine nucleotide regulatory protein. This guanine nucleotide regulatory protein, movement of the receptor-ligand complex, and the signals generated by the two second messengers, IP3 and DG, interact in a complex manner to cause an integrated response of vascular smooth muscle to angiotensin II stimulation.
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PMID:Angiotensin II stimulation of vascular smooth muscle cells. Secondary signalling mechanisms. 267 2

The effects of islet-activating protein (pertussis toxin) on bradykinin-mediated inositol trisphosphate labeling, prostaglandin E2 production, and calcium mobilization in rabbit renal papillary collecting tubule cells were assessed. Islet-activating protein induced time and concentration-dependent decreases in bradykinin-stimulated prostaglandin E2 production. Islet-activating protein induced increases in basal cyclic AMP levels but not in arginine vasopressin-stimulated cAMP. This effect could be inhibited by prior incubation with 2',5'-dideoxyadenosine, an inhibitor of adenylate cyclase. Although cAMP and cAMP analogues were able to inhibit both basal and bradykinin-stimulated prostaglandin E2 formation, the inhibitory effects of islet-activating protein on prostaglandin E2 formation and inositol trisphosphate labeling were observed in the presence of dideoxyadenosine. Moreover, islet-activating protein lowered both the basal and kinin-stimulated cytosolic calcium concentration as assessed by Quin 2 fluorescence. Finally, incubation of a membrane fraction of papillary cells with islet-activating protein resulted in the ADP-ribosylation of a 39/41-kDa doublet. These data support the role of a guanine nucleotide regulatory protein in bradykinin-mediated signal transduction in rabbit papillary collecting tubule cells.
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PMID:Islet activating protein inhibits kinin-stimulated inositol phosphate production, calcium mobilization, and prostaglandin E2 synthesis in renal papillary collecting tubule cells independent of cyclic AMP. 282 14

Surface stimulation of fresh or cultured human mononuclear cells by latex particles causes an increase in the accumulation of cyclic AMP that is inhibited by preincubation with calcitonin (CT). Preincubation of cultured monocytes with 500 ng/ml pertussis toxin totally blocks the inhibitory effects of CT at low concentrations of this hormone. The effects of pertussis toxin are dose-related and eliminated by boiling the toxin. Similar preincubations with cholera toxin have no significant effects on subsequent inhibition of surface-stimulated cyclic AMP by CT. Membranes prepared from cultured human monocytes contain a 41,000-dalton protein that is ADP-ribosylated by pertussis toxin and may be the inhibitory guanine nucleotide regulatory protein (Ni) mediating this inhibition.
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PMID:Pertussis toxin blocks the inhibitory effects of calcitonin on cyclic AMP accumulation in stimulated cultured human monocytes. 282 46

Y1 adrenal tumor cells are resistant to the steroidogenic effect of A-II though they possess specific A-II binding sites. The number of these binding sites is lower in Y1 cells than in bovine adrenal cells, but the affinity is similar in the two models. Moreover, Y1 cells are shown to contain a high level of cytosolic protein kinase C whose properties appear similar to those observed in bovine adrenal cells. However, the activation of protein kinase C by a phorbol ester (PMA) or diacylglycerol (OAG) does not induce steroidogenesis in Y1 cells. On the other hand, A-II, without any effect on adenylate cyclase in basal conditions, reduces the ACTH-induced cAMP production in Y1 cells. This inhibitory effect of A-II is not blocked by phosphodiesterase inhibitor but is completely abolished after 24 hours of pretreatment of intact cells with pertussis toxin. This inhibition is probably mediated by the inhibitory guanine nucleotide regulatory protein (Gi) since the labeled 41 KD-ADP ribosylated protein disappeared after 24 hours of pretreatment of intact cells with pertussis toxin. Moreover, the accumulation of inositol phosphates under A-II stimulation was low, which suggests that the coupling of A-II receptors with phospholipase C is reduced in Y1 cells. The Y1 cell line is probably a good model to study the post membrane events in A-II action.
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PMID:Angiotensin II (A-II) steroidogenic refractoriness in Y-1 cells in the presence of A-II receptors negatively coupled to adenylate cyclase. 282 18

Prostaglandin E1 (PGE1) at 1 nM inhibits arginine-vasopressin (AVP)-induced water reabsorption in the rabbit cortical collecting tubule (RCCT), while 100 nM PGE1, by itself, stimulates water reabsorption (Grantham, J. J., and Orloff, J. (1968) J. Clin. Invest. 47, 1154-1161). To investigate the basis for these two responses, we measured the effects of prostaglandins on cAMP metabolism in purified RCCT cells. In freshly isolated cells, PGE2, PGE1, and 16,16-dimethyl-PGE2 acting at high concentrations (0.1-10 microM) stimulated cAMP accumulation; however, one PGE2 analog, sulprostone (16-phenoxy-17,18,19,20-tetranor-PGE2 methylsulfonilamide), failed to stimulate cAMP accumulation or to antagonize PGE2-induced cAMP formation; PGD2, PGF2 alpha, and a PGI2 analog, carbacyclin (6-carbaprostaglandin I2), also failed to stimulate cAMP synthesis. These results suggest that there is a PGE-specific stimulatory receptor in RCCT cells which mediates activation of adenylate cyclase. Occupancy of this receptor would be anticipated to cause water reabsorption by the collecting tubule. At lower concentrations (0.1-100 nM) PGE2, PGE1, 16,16-dimethyl-PGE2, and, in addition, sulprostone inhibited AVP-induced cAMP accumulation by fresh RCCT cells in the presence of cAMP phosphodiesterase inhibitors. Pertussis toxin pretreatment of RCCT cells blocked the ability of both PGE2 and sulprostone to inhibit AVP-induced cAMP accumulation. In membranes prepared from RCCT cells, sulprostone prevented stimulation of adenylate cyclase by AVP. These results suggest that E-series prostaglandins (including sulprostone) can act through an inhibitory PGE receptor(s) coupled to the inhibitory guanine nucleotide regulatory protein, Gi, to block AVP-induced cAMP synthesis by RCCT cells. Occupancy of this receptor would be expected to cause inhibition of AVP-induced water reabsorption in the intact tubule. Curiously, after RCCT cells were cultured for 5-7 days, PGE2 no longer inhibited AVP-induced cAMP accumulation, but PGE2 by itself could still stimulate cAMP accumulation. In contrast to PGE2, epinephrine acting via an alpha 2-adrenergic, Gi-linked mechanism did block AVP-induced cAMP formation by cultured RCCT cells. This implies that some component of the inhibitory PGE response other than Gi is lost when RCCT cells are cultured.
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PMID:Regulation of cyclic AMP metabolism in rabbit cortical collecting tubule cells by prostaglandins. 283 64

The purpose of these studies was to determine how exposure to FSH affects subsequent responsiveness of adenylyl cyclase and progesterone production to FSH in immature porcine granulosa cells in vitro. Acute cAMP and progesterone responses to FSH and the postreceptor activators of cyclase, forskolin and cholera toxin, were determined after a 24-h preincubation with FSH. Pretreatment with FSH (1-1000 ng/ml) resulted in an increase in subsequent basal progesterone production which was dependent on preincubation FSH concentration. The cAMP response to FSH, on the other hand, was reduced after preincubation with FSH in a manner dependent on preincubation FSH concentration. Removal of FSH with acidified medium and subsequent incubation in FSH-free medium resulted in recovery of the cAMP response to FSH, indicating that attenuation of the response is reversible. Attenuation of the cAMP response to FSH does not appear to be due to 1) a loss of activity of the catalytic moiety of cyclase, since the response to forskolin and cholera toxin was not decreased by FSH; 2) a decrease in coupling of the stimulatory guanine nucleotide regulatory protein with the catalytic moiety of cyclase, since the response to cholera toxin was not reduced by FSH; 3) inhibitory signals, since preincubation with pertussis toxin did not affect the subsequent response to FSH; or 4) cAMP itself, since neither cholera toxin nor the cAMP analog 8-(4-chlorophenyl-thio)cAMP affected the response to FSH. It appears, instead, that FSH regulates FSH responsiveness by regulating the interaction of the FSH receptor with stimulatory guanine nucleotide regulatory protein.
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PMID:Autoregulation of acute progesterone and adenosine 3',5'-monophosphate responses to follicle-stimulating hormone (FSH) in porcine granulosa cells: effects of FSH, cholera toxin, forskolin, and pertussis toxin. 284 9


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